Is ANKAR p.Thr206Ala (c.616A>G) pathogenic?

ANKAR p.Thr206Ala (c.616A>G) is classified Benign in ANKAR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). AlphaMissense: likely benign (0.1566); Low-frequency (popmax 2.09%, afr).

How common is ANKAR p.Thr206Ala (c.616A>G) in the general population?

ANKAR p.Thr206Ala (c.616A>G) is low-frequency (popmax 2.09%, afr) (gnomAD).

What do computational predictors say about ANKAR p.Thr206Ala (c.616A>G)?

AlphaMissense predicts likely benign (score 0.1566) — an in-silico prediction, not a clinical call.

ANKAR p.Thr206Ala

c.616A>G · rs144939402 · VCV716762

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1566 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.09%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1566	likely benign
REVEL	0.037	moderately benign-leaning
SaProt	LLR -5.48	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 70 kb · p 0.0059 · regional, not allelic
Overall
CADD	19.55	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.09% African / African-American · 1,527/73,106 alleles

Filtering AF 2% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.97%

Overall 0.11% 1,742/1,577,898 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.09%	48
Remaining individualsnot grpmax-eligible	0.161%	621
Admixed American	0.154%	649
Middle Eastern	0.0511%	1,955
South Asian	0.0142%	7,062
European (non-Finnish)	0.00197%	50,698

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ANKAR
Protein: p.Thr206Ala
Coding: c.616A>G
MANE Select: NM_001378068
dbSNP: rs144939402
Type: single nucleotide variant
Location: chr2:189689541 (GRCh38)
Gene constraint: LOEUF 1.07 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.79

Full ANKAR gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANKAR p.Asn938= Benign ★★ same type
ANKAR p.Gln1419Leu Benign ★★ same type
ANKAR p.Ile1349= Benign ★★ same type
ANKAR p.Leu94Arg Benign ★★ same type
ANKAR p.Thr92= Benign ★★ same type
ANKAR p.Tyr1262Ser Benign ★★ same type
ANKAR p.Val776Ala Likely benign ★★ ⚠ same type
OSGEPL1 p.Asn27His Benign ★★ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/ankar-p-thr206ala (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown